A Randomized Phase 2 Study of Atezolizumab With or Without Selinexor in Alveolar Soft Part Sarcoma (AXIOM)
PRIMARY OBJECTIVE:
I. Determine the overall response rate (by Response Evaluation Criteria in Solid Tumors
[RECIST] version [v]1.1) for selinexor in combination with atezolizumab in immune checkpoint
inhibitor (ICI)-naive patients with alveolar soft part sarcoma (ASPS).
SECONDARY OBJECTIVE:
I. Assess the number of activated CD8+ T cells infiltrating the tumor before and after
atezolizumab + selinexor combination treatment, and correlate treatment-induced changes with
clinical response.
EXPLORATORY OBJECTIVES:
I. Compare RECIST v 1.1 versus (vs) immune RECIST (iRECIST) in patients with ASPS on
atezolizumab + selinexor.
II. Examine changes in PD-1/PD-L1 expression in the tumor microenvironment before and after
atezolizumab + selinexor treatment, and correlate treatment-induced changes with clinical
response.
III. Evaluate potential associations between atezolizumab + selinexor activity and tumor
genomic alterations.
OUTLINE: This is a randomized phase 2 trial that incorporates a safety run-in of the
selinexor in combination with atexolizumab. After the safety run-in phase, patients are
randomized to 1 of 2 arms. Patients with advanced soft tissue sarcoma are assigned to Arm I.
ARM I: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 8 of cycle
1, and then on day 1 of subsequent cycles. Patients also receive selinexor orally (PO) once
weekly (QW) on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of
disease progression or unacceptable toxicity. Patients also undergo biopsy at baseline, cycle
1 day 8 and cycle 3 day 1, computed tomography (CT) and magnetic resonance imaging (MRI) at
baseline, end of cycle 2, and every 2 cycles thereafter, and collection of blood samples
throughout the study.
ARM II: Patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Cycles
repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients
with disease progression may crossover to Arm I. Patients also undergo biopsy at baseline and
cycle 3 day 1, CT and MRI at baseline, end of cycle 2, and every 2 cycles thereafter, and
collection of blood samples throughout the study.
After completion of study treatment, participants are followed up for 30 days.
A Phase 1/1b Study of CHS-388 (Formerly Known as SRF388) in Patients With Advanced Solid Tumors
This is a Phase 1/1b, open-label, first-in-human (FIH), dose-escalation and expansion study
of CHS-388, a monoclonal antibody targeting IL-27, as a monotherapy and in combination in
patients with solid tumors that will be conducted in 4 parts:
- Part A: CHS-388 monotherapy dose-escalation portion of the study will evaluate the
safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of CHS-388 as
monotherapy in patients with advanced solid tumors.
- Part B: CHS-388 monotherapy expansion cohorts will evaluate the safety, efficacy,
tolerability, PK, and pharmacodynamics of CHS-388 monotherapy in patients with advanced
or metastatic ccRCC, advanced or metastatic HCC, and advanced or metastatic NSCLC in
indication specific cohorts.
- Part C will evaluate the safety, preliminary efficacy, tolerability, and PK of CHS-388
in combination with pembrolizumab in patients with advanced RCC,HCC, or NSCLC.
- Part D will evaluate the safety, preliminary efficacy, tolerability, and PK of CHS-388
in combination with toripalimab in patients with advanced NSCLC.
A Phase 1/2 Study Investigating the Safety and Efficacy of Autologous TAC T Cells in Subjects With Unresectable, Locally Advanced or Metastatic Claudin 18.2+ Solid Tumors
The TAC technology is a novel approach to modifying T cells, herein referred to as TAC T
cells, and using them in the treatment of solid tumors. TAC T cells are produced through
genetic engineering, incorporating TAC receptors into a patient's own T cells. This redirects
these enhanced T cells to specific cancer antigens, and upon recognition, activates them
through the natural signaling pathways of the endogenous TCR.
In the TAC01-CLDN18.2 engineered T cell product; TAC T cells recognize the CLDN18.2, a tight
junction protein present on the surface of tumor cells, where the protein expression is no
longer limited to tight junctions and are visible to T cells to eradicate them. Consequently,
it is hypothesized TAC01-CLDN18.2 will be potentially safe and active in treating patients
with CLDN18.2+ solid tumors and provide a clinically meaningful therapeutic benefit in
patient populations with high unmet medical need.
This is a first-in-human study investigating TAC01-CLDN18.2 to evaluate the safety, MTD or
RP2D, PK, and efficacy in subjects with CLDN18.2+ solid tumors who have been treated with at
least 2 lines of prior therapy in Phase 1 and after at least 2 lines and no more than 4 lines
of prior therapy in Phase 2 (Note: in each phase, subjects with PDAC may have been treated
with 1 line of prior antineoplastic therapy. In addition, subjects who are being treated with
current lines of therapy, but not deriving benefit or not tolerating therapy, and have not
progressed maybe also eligible as long as they have measurable disease at baseline as a
starting reference point). In Phase 1, escalating doses of TAC01-CLDN18.2 will be evaluated
to identify the RP2D using the classic 3+3 dose escalation study design.
In Phase 2, dose expansion groups will further evaluate the efficacy, safety, and PK of the
MTD or RP2D for TAC01-CLDN18.2 in subjects with gastric and esophageal AC (Group A), PDAC
(Group B), and mucinous ovarian and NSCLC cancers (Group C). In Phase 2, definitions of
eligible CLDN18.2+ IHC expression levels will be based on analysis of data from Phase 1 for
signals of clinical activity since there are no formal CAP/ASCO guidelines for CLDN18.2+
expression levels. In Phase 2, a Simon 2-stage design will be used to enroll up to 57
subjects in Group A and 22 subjects in Group C. Group B (PDAC) will enroll up to 10 subjects
as an exploratory cohort due to the historically low ORRs observed in PDAC. The 10 treated
subjects in Group B are designed to seek evidence of potential clinical activity in this
difficult to treat CLDN18.2+ subpopulation of PDAC.
Randomized Phase 2b Study of Safety And Efficacy Of TVI-Brain-1 Combined With Conformal Radiotherapy And Temozolomide Vs Standard Therapy In Newly Diagnosed MGMT Negative Glioblastoma Multiforme (GBM)
This randomized study is designed to compare the combination of TVI-Brain-1 immunotherapy and
standard therapy compared to standard therapy alone as a treatment for newly diagnosed MGMT
unmethylated glioblastoma patients. The general procedures include the collection and testing
of cancer tissue samples after surgery and chemoradiation therapy (radiation and
temozolomide). For the patients randomized into the investigational study treatment group,
they will also receive two vaccinations created from their own cancer cells, undergo
leukapheresis to collect immune T-cells from their blood, and transfer of those activated
effector T-cells after chemoradiation therapy. All patients are followed with MRIs at
follow-up visits.
A Phase 1/2 Study of EG-70 as an Intravesical Administration to Patients With BCG Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC) and High-Risk NMIBC Patients Who Are BCG Naïve or Received Incomplete BCG Treatment
EG-70 is a novel non-viral gene therapy. EG-70 is designed to elicit a local immune response
following delivery of the study gene therapy to the bladder urothelium. This approach of
local administration through bladder instillation has the potential to induce a potent immune
response exclusively at the site of the tumor, resulting in greater therapeutic benefit while
reducing undesirable systemic toxicity.
Eligible BCG-unresponsive NMIBC patients will be enrolled in Phase 1, and Cohort 1 of Phase
2. Eligible high-risk NMIBC patients who have been incompletely treated or are BCG-naïve will
be enrolled starting in Phase 2 in a separate single-arm cohort (Cohort 2).
Patients will be treated for up to four 12-week cycles of study drug instillation doses and
assessments with follow up assessments.
A Phase I/II, Multicenter, Open-Label Study of Nous-209 Genetic Vaccine for the Treatment of Microsatellite Unstable Solid Tumors
Ref: Protocol v9.0, dated 7Nov2023. Both Frame Shift Peptide (FSP) neoantigen-encoding
genetic vaccines are administered intramuscularly using 1 prime with the GAd20-209-FSP and 3
boosts with MVA-209-FSP in combination with Keytruda®, the licensed programmed death
receptor-1 (PD-1)-blocking antibody pembrolizumab, in adult subjects with unresectable or
metastatic Mismatch Repair Deficient (dMMR) or MSI-H colorectal cancer (CRC), gastric, or G-E
junction tumors. In Phase I, GAd20-209-FSP prime will be administered on the day of 2nd
pembrolizumab infusion (week 4); MVA-209-FSP boosts will be administered on the day of 3rd,
4th and 5th pembrolizumab infusion (weeks 7 and 10 and 13). In Phase II, GAd20-209-FSP prime
will be administered on the same day as the 1st pembrolizumab infusion (day 1, week 1);
MVA-209-FSP boosts will be administered in week 2 and at the time of the 2nd and 3rd
pembrolizumab infusions (weeks 4 and 7).
The study is composed of a Phase I divided in two parts and a Phase II, as described below :
Phase I:
- Cohort A - Dose escalation Cohort of Nous-209 vaccine plus pembrolizumab combination
therapy in adult subjects with unresectable or metastatic deficient mismatch repair
(dMMR) or MSI-H CRC, gastric, or gastro-esophageal junction (G-E junction) tumors;
- Cohort B - Expansion Cohort at Recommended Phase 2 Dose (RP2D) of Nous-209 vaccine plus
pembrolizumab combination therapy in adult subjects with unresectable or metastatic dMMR
or MSI-H CRC, gastric, or G-E junction tumors. Part 2 - Extended Follow-up from week 27
to week 110.
Phase I (Cohorts A and B): The Sponsor estimates that the trial will require approximately 24
months from the time the first subject signs the informed consent until the last subject's
last visit at week 26 (Main Study); and approximately 42 months until last subject's last
visit at week 110 (Extended follow up).
Phase II:
Expansion at RP2D of Nous-209 vaccine plus Keytruda® (pembrolizumab) combination therapy in
adult subjects in the following study population:
- Cohort C (Phase II) - Subjects with locally advanced unresectable or metastatic,
microsatellite instability high (MSI-H) or dMMR CRC who are eligible for anti-PD-1 1st
line of treatment. Subjects will be randomized with an allocation ratio 2:1 to Nous-209
vaccine plus pembrolizumab combination therapy versus pembrolizumab monotherapy.
- Cohort D (Phase II) - Subjects with locally advanced unresectable or metastatic,
microsatellite instability high (MSI-H) or dMMR CRC who have had radiographic
progression (PD) after having a best response of stable disease (SD) or better on/after
anti-PD1 treatment.
Phase II (Cohorts C and D): Participation duration per subject is expected to last up to 18
months in Cohort C and up to 12 months in Cohort D.
Subjects who do not progress might stay in extended follow-up for up to approximately 2 years
(106 weeks or completion of 35 administrations of pembrolizumab).
Enrollment in Phase I is now terminated, and in Phase II is ongoing.
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